Main author: Arsalan Amirfallah
Institution or Company: University of Iceland, Faculty of Medicine, Bio medical Research Center, Landspitali, Department of pathology/cell biology unit
Co-Authors, Institution or Company:
Hildur Knútsdóttir, Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD. Aðalgeir Arason, Molecular Pathology, Department of Pathology, Landspitali, Biomedical Center. Bylgja Hilmarsdóttir, Molecular Pathology, Department of Pathology, Landspitali, Biomedical Center. Óskar Þór Jóhannsson, Oncology Department, Landspitali. Bjarni A. Agnarsson, Department of Pathology, Landspitali, Medical Department, University of Iceland. Rósa Björk Barkardóttir, Molecular Pathology, Department of Pathology, Landspitali, Biomedical Center. Inga Reynisdóttir, University of Iceland, Faculty of Medicine, Bio medical Research Center, Landspitali, Department of pathology/cell biology unit.
Introduction: The effects of MIR21 gene have been attributed to miR-21-5p, but its sibling strand, miR-21-3p, has received little attention as a potential progression-related breast cancer gene. This study aimed to analyze if miR-21-3p expression was associated with characteristics that can predict patient prognosis.
Methods: MiR-21-3p levels were quantified in two breast cancer cohorts (n=139, n=281) and its levels were correlated with clinical and pathological factors as well as the patients’ survival. The results were followed up in two publicly available breast cancer cohorts (n=946, n=1174). Correlation between miR-21-3p expression and mRNAs quantity in the patients´ tumors were also analyzed and compared to miR-21-3p target genes from miRTarBase.
Results: The results show that miR-21-3p expression was significantly higher in large breast tumors (> 20 mm, p = 0.022), tumors with high grade (p = 3.68*10-14), tumors from patients with positive lymph nodes (p = 0.001) and tumors that expressed the HER2 receptor (p = 2.63*10-9). Patients with high miR-21-3p expression in breast tumors had shorter breast cancer-specific survival than those with low expression (log-rank p = 0.002), even if corrected for tumor characteristics. The three most significantly downregulated genes that miR-21-3p correlated with have been confirmed as its targets.
Conclusion: The results indicate that high miR-21-3p expression is associated with a worse prognosis for breast cancer patients and it affects pathways that support breast tumor proliferation.
